Versatile Biocatalytic C(<i>sp</i><sup>3</sup>)−H Oxyfunctionalization for the Site‐ Selective and Stereodivergent Synthesis of α‐ and β‐Hydroxy Acids
Yingle Mao, Weijie Zhang, Zunyun Fu, Yanqiong Liu, Lin Chen, Xin Lian, Dan Zhuo, Jiewei Wu, Mingyue Zheng, Cangsong Liao
Abstract
Abstract C( sp 3 )−H oxyfunctionalization, the insertion of an O‐atom into C( sp 3 )−H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C( sp 3 )−H oxyfunctionalization has the potential to overcome limitations inherent to small‐molecule‐mediated approaches by delivering catalyst‐controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α ‐ketoglutarate‐dependent iron dioxygenases that catalyze the site‐ and stereodivergent oxyfunctionalization of secondary and tertiary C( sp 3 )−H bonds, providing concise synthetic routes towards four types of 92 α ‐ and β ‐hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.